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Which of the following is correct in relation to BRCA1/2 mutations and breast cancer?

The lifetime risk (by age 70) of developing breast cancer for BRCA1 mutation carriers can be as high as 80%.
(Correct. BRCA mutations carry a 50% to 80% lifetime risk of female breast cancer, a 6% lifetime risk of male breast cancer (BRCA2), and a 15% to 25% lifetime risk of ovarian cancer. BRCA1 mutation carriers are more likely to present with breast cancer at a lower age than BRCA2 mutation carriers (peak incidence at 45-49 years and 65-69 years, respectively). It is important to understand these statistics when considering either genetic testing or prevention strategies in a known BRCA mutation carrier.)

Which of the following treatments has been shown to provide relief of symptoms in more than 50% of patients with cyclical breast pain?

Evening primrose oil

The most common histologic type of invasive breast cancer is which of the following?

Ductal adenocarcinoma.

Hormone regulation of mammary epithelial development includes:

Initiation of ductal development by estrogen.

Which benign breast disease is associated with an increased risk of malignancy?

Atypical ductal hyperplasia

Which of the following statements regarding steroid hormones and breast cancer is correct?
- The kidney is the principle site of steroid metabolism.
- The rate-limiting step of steroid hormone biosynthesis involves the conversion of pregnenolone to progesterone.
- In postmenopausal women, androgens are produced in the adrenal gland, and adipose tissue is the principal site for aromatization.
- Circulating steroid hormones are primarily lipid-bound and are thus considered "bioavailable."

In postmenopausal women, androgens are produced in the adrenal gland, and adipose tissue is the principal site for aromatization.
(In postmenopausal women, androgens are produced in the adrenal gland, and adipose tissue is the principal site for aromatization. Normal adipose tissue uses promoter I.4 of the CYP19 gene to stimulate aromatase production; however, breast tumors and their surrounding adipose tissue activate promotor II of the CYP19 gene, and the result is a greater expression of aromatase. AIs can reduce estrogen production by more than 90% and are classified according to the specificity, potency, and reversibility with which they inhibit the aromatase enzyme.)

Which of the following histologic breast changes is most associated with an increased risk of breast cancer?
- Epithelial hyperplasia with atypia.
- Macro- and microcysts.
- Apocrine metaplasia.
- Fibroadenoma.
- Duct ectasia.

Epithelial hyperplasia with atypia.

Paget disease of the breast

Paget disease is nearly always detectable on clinical examination as a crusting erosion of the nipple. It may be less subtle presenting with thickening redness or roughness of the nipple, often associated with itching and burning. It is often associated with subareolar intraductal cancer. Survival is dependent upon the stage of the accompanying breast cancer.

A 42-year-old, otherwise healthy woman has a new, 1-cm in diameter density deep in the central retroareolar region of her right breast on mammography. She has no palpable abnormality on physical examination. No lesion is detected on ultrasonography. The best diagnostic option is

stereotactic core needle biopsy of the breast

A 32-year old male presents to clinic due to enlarging left breast. He states that he has noticed this "swelling" for the past year but has only sought medical care now because it has becoming noticeably larger than his right breast. He denies pain or nipple discharge. He denies family history of breast cancer in either women or men in his immediate or distant family and steroid use. On examination, the patient is very muscular with a smooth right breast, devoid of masses. His left breast is noted to have rubbery mass extending concentrically from the nipple. His testicular exam is normal. What is the appropriate management of this patient?

Mammogram and ultrasound
(Male breast cancer is rare, but gynecomastia is common, Gyenocmastia has frequently been associated with estrogen excess or testosterone deficiency. Radiologic evaluation includes diagnositic mammography and ultrasound. Mammography may be helpful to rule out findings such as abnormal micro- calcifications that may suggest cancer.)

All of the following statements about male breast cancer are true except:
- It is highly responsive to hormonal therapy and orchiectomy.
- Risk is increased with mumps orchitis in men older than 20 years.
- The majority are histopathologically ductal carcinoma.
- It has a clear relationship to gynecomastia.
- Hormonal induction may be etiologic in Klinefelter syndrome.

It has a clear relationship to gynecomastia.

regarding diagnosis of breast disease...

Physical examination alone is unspecific.
(Both benign and malignant breast disease may present as a lump in the breast. Ninety percent of new lumps in premenopausal women are benign. A tumor is more likely to be hard and immobile with irregular edges. However, physical examination alone is unspecific and all masses should be evaluated in context of history, examination, and investigations.)

Which of the following statements concerning normal breast development and physiology is incorrect?
- Fibrocystic change is associated with an increased risk of breast cancer.
- Breast development before 8 years of age (premature thelarche, precocious puberty) is abnormal.
- Lactogenesis occurs in two stages and is dependent on prolactin and glucocorticoids.
- In postmenopausal women, the principal source of circulating estrogen (primarily estradiol) is conversion of adrenally generated androstenedione to estrone by aromatase in peripheral tissues with further conversion of estrone to estradiol.
- At birth, there are no clear morphologic or physiologic differences between the sexes.

Fibrocystic change is associated with an increased risk of breast cancer.
(Fibrocystic change represents a wide range of clinical and histologic findings. First presenting at menarche and typically resolving after menopause, it is believed to reflect an exaggerated response to circulating hormones and their effect on breast proliferation. Fibrocystic change is not associated with an increased risk of breast cancer.)

Which of the following statements is incorrect regarding the lymphatic drainage of the breast?
- All four quadrants of the breast drain as a unit to a few common nodes in the axilla.
- ALND is an important component of locoregional control.
- Lymphedema is an unfortunate complication of ALND affecting up to 50% of patients.
- The "level" of axillary node group is determined by the relation of the nodes to the pectoralis muscle.
- The lymphatics of the skin overlying the breast are in direct contact with the underlying deeper lymphatics.

Lymphedema is an unfortunate complication of ALND affecting up to 50% of patients.
(Lymphedema affects between 10% and 15% of patients undergoing ALND.)

Which of the following (comedocarcinoma, LCIS, radial scar, phyllodes tumor, DCIS) is least likely to be diagnosed by mammography?

Lobular carcinoma in situ

Which of the following is incorrect in relation to BRCA1/2 mutations and breast cancer?
- Functional roles of BRCA1 and BRCA2 include DNA repair, cell-cycle checkpoints, and apoptosis, and suggest that the BRCA genes function as "caretakers."
- BRCA 1 and 2 are considered tumor suppressor genes and thus follow Knudsen 2-hit hypothesis.
- Reproductive factors have been implicated in BRCA tumorigenesis.
- BRCA mutations are inherited in an autosomal recessive pattern with low penetrance.
- The wide variation in cancer risk among women with BRCA1/2 mutations can be by different mutations of the gene(s).

BRCA mutations are inherited in an autosomal recessive pattern with low penetrance.

regarding LCIS...

With the exception of patients with a BRCA mutation, LCIS confers the greatest risk known for the development of subsequent invasive disease.
(Unlike DCIS, LCIS is not an obligate precursor for invasive disease. It is considered a "high-risk factor" that confers an increased rate of developing invasive disease (approximately 1%-2% a year, and 30%-40% lifetime) (188). Both invasive-ductal and lobular cancer can occur with LCIS. The risk can persist for up to 30 years; however, studies report that most of the cancers occur between years 15 and 30 postdiagnosis.)

regarding infiltrating lobular carcinoma...

It has a high incidence of multicentricity.

benign breast disease

Hormones are potential causal factors in benign breast disease.

The myoepithelial cells in the breast of the nonpregnant, premenopausal adult female...

Are stimulated to contract by sex steroids and prolactin.

During a modified mastectomy and axillary dissection, which of the following nerves, if divided, produces the least significant morbidity?
- Long thoracic nerve (respiratory nerve of Bell).
- Intercostal brachial nerve.
- Lateral pectoral nerve.
- Axillary nerve.
- Thoracodorsal nerve.

Intercostal brachial nerve.
(This results in loss of skin sensation in the upper inner arm.)

tumor growth kinetics and metastasis

The p53 gene is an important regulator of the cell cycle. p53 mutations are the most common mutations associated with Li-Fraumeni syndrome.
(Li-Fraumeni syndrome is a breast cancer susceptibility condition associated with a high incidence of leukaemia, lymphoma, osteosarcomas, and adrenocortical carcinomas that is thought to be due to a point mutation of the p53 gene.)

Which of the following is false regarding primary nonepithelial cancer of the breast?
- Metastatic disease is associated with up to 20% of patients with cytosarcoma phyllodes.
- Classical microscopic features include a leaf-like architecture consisting of elongated cleft-like spaces that contain papillary projections of epithelial-lined stroma with varying degrees of hyperplasia and atypia.
- Cytosarcoma phyllodes are the most common nonepithelial tumors of the breast.
- Primary lymphoma of the breast accounts for less than 1% of all extranodal lymphomas. The vast majority are non-Hodgkin lymphomas.
- Stewart-Treves syndrome is defined by lymphangiosarcomas of the upper extremity, breast, and axilla arising in women with chronic lymphedema after breast cancer therapy.

Metastatic disease is associated with up to 20% of patients with cytosarcoma phyllodes.
(Metastatic disease seems to be rare, with a reported rate of less than 5% of all PTs, and survival rates with metastatic disease can vary greatly.)

Which of the following arteries supplies more than 50% of the nutrient blood flow to the breast?

Internal mammary artery.
(This artery supplies approximately 60% of the total breast mass with blood flow.)

A 39-year-old woman has a 1x1x1-cm focus of microcalcifications in the lower outer quadrant of her left breast. No mass is palpable. Stereotactic core biopsy shows ductal carcinoma in situ, non-comedo type. The next step in management should be

wide excision of the microcalcifications with assessment of the margins

Re: the microenvironment and angiogenesis, how does imatinib inhibit tumorigenesis?

By targeting kinases such as bcr-abl kinase, c-KIT tyrosine kinase, and the platelet-derived growth factor (PDGF) tyrosine-kinase
(Therapeutic targeting of the tumor microenvironment has been developed. Most of these agents are in phase I or II clinical trials, but one has been approved by the FDA. Imatinib, initially named signal transduction inhibitor-571 (STI-571), targets pericytes and stromal fibroblasts, and is a specific blocker of bcr-abl kinase, c-KIT tyrosine kinase, and the platelet-derived growth factor (PDGF) tyrosine-kinase receptor. Initially approved for use in patients with chronic myeloid leukemia, currently a phase II clinical trial is investigating the affect of docetaxel plus imatinib in metastatic breast cancer. Such agents hold promise in a multimodal approach to treatment.)

One week after a postoperative visit for drain removal following modified radical mastectomy, a 45-year-old woman has a 6-cm, nontender axillary mass. She has a temperature of 37.9 C (100.2 F) and a well healed mastectomy incision and drain sites. The most appropriate initial management is

needle aspiration of the mass

Which of the following statements concerning steroid hormone receptors is incorrect?
- The expression levels of the p160 steroid coactivator family are generally ubiquitous throughout difference tissue- and cell-types.
- Both the ER and the PR consist of two isoforms.
- For patients with breast cancer, the ER and PR status holds both prognostic and predictive significance.
- The role of the AR in breast cancer remains unclear.
- All members of the NR superfamily share several conserved structural elements as well as functional domains.

The expression levels of the p160 steroid coactivator family are generally ubiquitous throughout difference tissue- and cell-types.
(The p160 steroid coactivator gene family contains three homologous members (SRC-1, SRC-2, SRC-3/AIB) that serve as transcriptional coactivators for steroid receptors such as the ER, PR, and AR. Found in many cell types, their expression levels are tissue- and cell-type dependent and, by virtue of their relative concentrations, they act as control mechanisms of the steroid receptor.)

Compared with estrogen receptor-negative breast tumors, estrogen receptor-positive (greater than 100 fmol/mg protein) breast tumors are more likely to be

lower S-phase and diploid

During pregnancy, all of the following changes occur in the breast except:
- An increase in the amount of adipose tissue relative to the glandular tissue.
- An increase in the number of myoepithelial cells.
- Ductal proliferation and branching.
- Activation of the "A" cells.
- An increase in the number of lobules.

An increase in the amount of adipose tissue relative to the glandular tissue.

epidermal growth factor (EGF) receptors

transmembrane, ligand-bound tyrosine kinase receptors
(The epidermal growth factor (EGF) receptors are transmembrane, ligand-bound tyrosine kinase receptors. There are four homologous members in the family (HER1-4), all of which have two functional domains (cytoplasmic tyrosine kinase domain and an Src-homology domain, SH-2 and SH-3). Interaction between the receptor, the ligand, and intracellular proteins is regulated by phosphorylation of the C-terminal tyrosine kinase residues.)

the microscopic anatomy of the breast

- Almost all breast cancers are malignant proliferations of epithelial cells
- The basement membrane is a bilayered structure comprising primarily of collagen and laminin.
- The glandular epithelium of the breast is composed of a single type of epithelial cell.
- Mammography (MG) can be limited by density of the breast tissue.
The breast is composed of glandular epithelium, fibrous stroma, connective tissue, and fat. The relative contribution of these tissues is under the control of circulating hormones (namely estrogen, progesterone, and prolactin) and as such, varies according to age, menstrual cycle, pregnancy, parity and breast feeding.

Polypeptides isolated from human breast cancers, which may participate in modulation of cell growth

Fibroblast growth factor, Epidermal growth factor (EGF T-1), Insulin-like growth factor (IGF-1), Transforming growth factor, type β.

DCIS with "microinvasion"

a predominantly in situ lesion that has less than 100 μm of malignant cells beyond the BM of the involved duct on light microscopy

The lymph nodes of the axilla are divided into three groups called levels I, II, and III. The anatomic landmark that defines these groupings is:

The pectoralis minor muscle.
(Level I nodes are located lateral to the pectoralis minor, level II nodes are located deep to the pectoralis minor muscle, and level III nodes are located medial to the muscle.)

mammary duct ectasia

Also known as plasma cell mastitis.

In a 60-year-old woman, fine-needle aspiration biopsy of a 1-cm in diameter breast mass shows infiltrating ductal carcinoma. At the minimum, therapy should include

partial mastectomy, sentinel lymph node biopsy, and radiation therapy to the breast

The accessory glands of Montgomery

Regress at menopause

The estrogen-receptor status of a breast tumor correlates with which of the following

Age of the patient.
(The ER protein quantity is lower and less frequently positive in premenopausal than in postmenopausal patients.)

A 42-year-old woman with a history of "fibrocystic disease" undergoes excision of microcalcifications in her breast which were detected on mammography. The histologic finding associated with the highest risk of developing subsequent breast cancer is

atypical ductal hyperplasia

the blood supply to the breast

Extensive collateralization occurs between many blood vessels within the breast.
(Extensive collateralization occurs between many vessels within the breast tissue, namely the internal mammary artery (IMA), the thoracoacromial artery, the subscapular artery, the upper thoracic artery, and the thoracodorsal vessels.)

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